1. Field of Invention
This invention relates to the treatment of cartilage and bone defects with biological materials manufactured in vitro. The invention also relates to the methods involved in producing the in vitro constituted biological materials.
2. Description of Prior Art
Over time, cartilage and bone loses the capacity to regenerate itself, making repair of articular cartilage and bone defects very difficult.
Heretofore a wide variety of methods have been proposed and implemented for healing cartilage and bone defects.
One such method for the treatment of cartilage defects consists of mechanically fixing a periosteal flap (bone skin) over the cartilage defect and implanting autologous cultured cartilage forming cells (chondrocytes) under the periosteal flap as described by Brittberg et al. "Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation," The New England Journal of Medicine 331:14, 889-895 (1994). Doctors regard this method as complicated with respect to the mechanical fixation of the periosteal graft and the injection of the cartilage forming cells (chondrocytes). The process requires skills and a considerable amount of practice. The process involves harvesting the periosteal graft from the proximal medial tibia which causes unwanted bleeding into the adjacent knee joint. A percentage of the injected cells are lost due to diffusion. In essence, doctors find the process as described by Brittberg et al. unsatisfactory because it is complicated, requires training, induces unwanted bleeding into the adjacent joint, and does not utilize all of the injected cells.
Other methods designed to treat cartilage defects involve grafting the defect with perichondrial and free periosteal grafts as described by Skoog et al. Skoog T. et al. "The formation of articular cartilage from free perichondrial grafts," Plastic and reconstructive Surgery 57:1, 1-6 (1976) and Rubak J. M. et al. "Chondrogenesis in repair of articular cartilage defects by free periosteal grafts in rabbits," Acta Orthop. 53:181-186 (1982). However, these techniques are unsatisfactory because they are limited by the amount of tissue available for grafting and the tendency toward ossification of the repair tissue.
Gendler EPO 739631A2 provides a method for producing a biological material comprising reconstituted cartilage tissue. His invention involves growing chondrocytes on a flexible sheet of 1.5 mm thick demineralized natural bone. This system will only demonstrate utility when the bone is non-self-derived because harvesting self-derived bone requires a complicated and painful surgery.
Atala et al. U.S. Pat. No. 5,516,532 provide a method for entrapping bone or cartilage cells in an organic polymer. The organic polymer is not a natural self-derived material which limits its utility. In addition, the cellular composite lacks the mechanical properties that are required for the treatment of cartilage and bone defects.
Barone et al. WO95/30383 propose methods for the production of a synthetic cartilage patch. Chondrocytes are manipulated in vitro to produce an endogenous synthetic matrix. Unfortunately, the synthetic matrix lacks the mechanical properties that are required for the treatment of cartilage defects located in the knee.
Approximately 20% of all bone fractures form a mechanically weak non-union. Repairing non-unions is a slow and painful process that might require three separate operations. Currently, the treatment of non-union bone fractures involves only surgical techniques. Nakahara et al. "Culture-expanded periosteal-derived cells exhibit osteochondrogenic potential in porous calcium phosphate ceramics in vivo," Clin Orthop 276:291-298 (1992) have suggested an experimental bone healing material comprising a porous calcium phosphate support and periosteal-derived cells. The system they describe for manufacturing the healing material is extremely complicated and comprises a unnatural synthetic support. The patient must resorb the support which might be associated with unforeseen, unwanted side-effects.
The current cartilage repair techniques require skills and causes bleeding into the knee or involve the use of mechanically weak non-self-derived material. The current bone repair techniques are not effective and time consuming. Therefore, most doctors would find it desirable to have alternative safe methods and materials to streamline and accelerate the treatment of cartilage and bone defects.